Heart failure is an abnormality in cardiac function that results from the inability of the heart to pump blood commensurate with the body's needs. Failure develops from a depression in myocardial contractility which can occur due to ischemic heart disease, hypertension, non-obstrusive cardiomyopathies and certain types of congenital heart disease.
As used herein, a cardiotonic agent is a substance which enhances the cardiac output, i.e. quantity of blood pumped by the heart of a mammal to which it is administered. It is advantageous to achieve such increased cardiac output with little or no increase in the rate of heartbeat of the mammal. This is accomplished by achieving a greater quantity of blood pumped by each beat of the heart.
Certain 2-(5-phenyl-2-furanyl)imidazoles are known, and it has been disclosed that some of these compounds have antidepressant, antihypertensive, or skeletal muscle relaxant activity. The following references disclose certain 2-(5-phenyl-2-furanyl)imidazoles and methods of synthesizing them and are hereby incorporated by reference: U.S. Pat. No. 4,012,414 issued to Pelosi on Mar. 15, 1977; U.S. Pat. No. 4,012,415 issued to Pelosi & Yu on Mar. 15, 1977; and U.S. Pat. No. 4,012,416 issued to Pelosi on Mar. 15, 1977.
South African patent application No. 813070 filed by Ciba-Geigy AG in the names of Fuhrer, Ostermayer, & Zimmermann, published May 26, 1982, discloses a group of 2-(3-carbamoyl-4-hydroxyphenoxy)ethylamino compounds that act in a specific manner on betaadrenergic receptors and exhibit cardiotonic activity. Among the many constituents disclosed in the reference that can be attached to this active center is an ((imidazol-2-yl)-2-furyl) phenoxy group. In Example II of the disclosure where synthesis of such a compound is described, several 2-(5-phenyl-2-furanyl)imidazoles are disclosed as intermediate compounds in the synthesis of the compounds of interest.
References which disclose compounds having structures similar to the (2-(5-phenyl-2-furanyl)imidazoles of the present invention include the following U.S. Pat. Nos. 3,927,023 issued to Brown & Shavel on Dec. 16, 1975; 3,993,643 issued to Henry & Cory on Nov. 23, 1976; 4,021,444 issued to Pelosi on May 3, 1977; 4,022,798 issued to Pelosi on May 10, 1977; 4,144,347 issued to Stern on Mar. 13, 1979; 4,289,526 issued to Worthington, de Fraine, Rathmel & Gatehouse on Sept. 15, 1981; and 4,411,908 issued to Chepleo & Myers on Oct. 25, 1983.
References which disclose certain cardiotonic agents include the following U.S. Pat. Nos. 3,985,891 issued to Kutter, Austel & Diederen on Oct. 12, 1976; 4,004,012 issued to Lesher & Opalka on Jan. 18, 1977; 4,032,575 issued to Ikezaki, Ito, Okazaki, Hoshiyama, Nagao & Nakajima on June 28, 1977; 4,289,772 issued to Campbell, Danilewicz, Evans & Ham on Sept. 15, 1981; 4,297,360 issued to Lesher, Opalka & Page on Oct. 27, 1981; 4,397,854 issued to Sircar on Aug. 9, 1983; and 4,405,635 issued to Schnettler, Dage & Crisar on Sept. 20, 1983.